Background: Kaposi sarcoma in people living with HIV (PLHIV) is the most common AIDS-associated malignancy. There is increased interest in Kaposi sarcoma in PLHIV with controlled HIV viremia. Objectives: To describe Kaposi sarcoma occurring in PLHIV despite virological control and to compare their clinical presentations with viremic AIDS-Kaposi sarcoma (AIDS-KS) and classic Kaposi sarcoma (CKS). Methods: This was a monocentric retrospective study, including all Kaposi sarcoma patients registered between the 1 January of 2000 and 31 December 2017 in a comprehensive data bank for all cancers in the Hérault region, South of France. AIDS-KS were also described using chart reviews from the Infectious diseases Department, which followed more than 90% of PLHIV from the same region. We defined aviremic AIDS-KS as Kaposi sarcoma occurring in persons taking HAART with a HIV viral load less than 50 copies for more than 12 months. We compared clinical characteristics of persons with aviremic AIDS-KS, viremic AIDS-KS and CKS, using the Kriegel score and number and topography of skin lesions, and presence of lymphedema. Results: We retrieved 187 Kaposi sarcoma cases, of which 12 occurred in PLHIV with aviremic AIDS-KS. Kriegel score stage I was found in 10 (83%) of the aviremic AIDS-KS, 34 (68%) of CKS and 38 (58.4%) of viremic AIDS-KS cases, with similar clinical presentations between aviremic AIDS-KS and CKS groups, and viremic AIDS-KS persons having more aggressive presentations. One person with aviremic AIDS-KS had visceral involvement. Conclusion: We showed that Kaposi sarcoma in PLHIV with controlled viremia were generally indolent, similarly to CKS. Visceral involvement is, however, possible.
Background Dupilumab is the first biotherapy available for the treatment of moderate-to-severe childhood atopic dermatitis (AD).Objective The aim of this study was to evaluate the effectiveness and safety of dupilumab in daily practice.Methods Patients aged 6-11, who had received a first dose of dupilumab, were included in this multicentre retrospective cohort study. The primary endpoint was change in SCORAD after 3 months of treatment. Secondary endpoints were change in IGA score at 3 months, proportion of patients with SCORAD50 and SCORAD75, description of adverse events and proportion of children in our cohort who would be excluded from pivotal phase 3 clinical trial.Results Eighty patients were included. After 3 months of treatment, there was a significant decrease in SCORAD (mean: 21.8 AE 13.8 vs 53.9 AE 18.5; P < 0.0001) and IGA (1.3 AE 0.8 vs 3.5 AE 0.7; P < 0.0001). Conjunctivitis was observed in 11.3% (n = 9/80); three patients experienced dupilumab facial redness (DFR); 17.5% (n = 14/80) reported injection site reactions; 6.3% (n = 5/80) discontinued treatment. 61.2% (n = 49/80) children were ineligible in the phase 3 trial. Limitations There is no control group. Because it was a real life study based on information from patient medical records in a French multicentre cohort, we cannot rule out the presence of reporting bias generated by the use of patient reported characteristics and missing information.
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Hemophagocytic lymphohistiocytosis (HLH) has been only rarely reported in patients with BRAF-mutated advanced melanoma treated with targeted therapies and never with first-line dabrafenib/trametinib combination thus far. Two patients treated with first-line dabrafenib and trametinib combination therapy for metastatic melanoma presented with sudden occurrence of fever, cytopenia, rhabdomyolysis, hepatic cytolysis, hypertriglyceridemia and very high ferritin levels after few weeks of treatment, associated with concomitant epstein-barr virus (EBV) reactivation in one patient. In both cases, drug-induced HLH was primarily considered owing to a high H-score and the absence of other etiology. Patients rapidly improved after treatment discontinuation associated with oral steroids in one patient and did not relapse after subsequent treatment resumption with a concurrent anti-BRAF/anti-MEK combination. In metastatic melanoma HLH may occur either spontaneously in the absence of any treatment as a paraneoplastic condition, related to an intercurrent infection or drug-induced mainly with various immunotherapy or with dabrafenib and trametinib following immunotherapy. However, such observations are scarce and these are the first cases of HLH occurring during first-line treatment with dabrafenib and trametinib in advanced melanoma to our knowledge. Pathomechanisms remain to be elucidated since triggering factors may encompass the treatment itself but also other significant actors including viral reactivation along with the underlying disease. The liability of treatment should be considered in cases of HLH occurring in patients with advanced melanoma successfully treated with a combined targeted therapy. A rechallenge with a concurrent anti-BRAF/anti-MEK can be proposed in this setting.
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